Abstract

The secretion of fluid, electrolytes, and protein by exocrine gland acinar cells is a vectorial process that requires the coordinated regulation of multiple channel and transporter proteins, signaling components, as well as mechanisms involved in vesicular fusion and water transport. Most critical in this is the regulation of cytosolic free [Ca2+] ([Ca2+]i) in response to neurotransmitter stimulation. Control of [Ca2+]i increase in specific regions of the cell is the main determinant of fluid and electrolyte secretion in salivary gland acinar cells as it regulates several major ion flux mechanisms as well as the water channel that are required for this process. Polarized [Ca2+]i signals are also essential for protein secretion in pancreatic acinar cells. Thus, the mechanisms that generate and modulate these compartmentalized [Ca2+]i signals are central to the regulation of exocrine secretion. These mechanisms include membrane receptors for neurotransmitters, intracellular Ca2+ release channels, Ca2+ entry channels, as well Ca2+ as pumps and mitochondria. The spatial arrangement of proteins involved in Ca2+ signaling is of primary significance in the generation of specific compartmentalized [Ca2+]i signals. Within these domains, both local and global [Ca2+]i changes are tightly controlled. Control of secretion is also dependent on the targeting of ion channels and transporters to specific domains in the cell where their regulation by [Ca2+]i signals is facilitated. Together, the polarized localization of Ca2+ signaling and secretory components drive vectorial secretion of fluid, electrolytes, and proteins in the exocrine salivary glands and pancreas. This review will discuss recent findings which have led to resolution of the molecular components underlying the spatio-temporal control of [Ca2+]i signals in exocrine gland cells and their role in secretion.

Keywords: Calcium homeostasis, calcium influx, ion channels, fluid secretion, salivary gland cells, physiology, knockout mouse models